Negative regulation of bacterial killing and inflammation by two novel CD16 ligands

Eur J Immunol. 2016 Aug;46(8):1926-35. doi: 10.1002/eji.201546118. Epub 2016 Jun 13.

Abstract

Sepsis, a leading cause of death worldwide, involves exacerbated proinflammatory responses and inefficient bacterial clearance. Phagocytic cells play a crucial part in the prevention of sepsis by clearing bacteria through host innate receptors. Here, we used a phage display library to identify two peptides in Escherichia coli that interact with host innate receptors. One of these peptides, encoded by the wzxE gene of E. coli K-12, was involved in the transbilayer movement of a trisaccharide-lipid intermediate in the assembly of enterobacterial common antigen. Peptide-receptor interactions induced CD16-mediated inhibitory immunoreceptor tyrosine-based activating motif signaling, blocking the production of ROS and bacterial killing. This CD16-mediated inhibitory signaling was abrogated in a WzxE(-/-) mutant of E. coli K-12, restoring the production of ROS and bacterial killing. Taken together, the two novel CD16 ligands identified negatively regulate bacterial killing and inflammation. Our findings may contribute toward the development of new immunotherapies for E. coli-mediated infectious diseases and inflammation.

Keywords: CD16; Escherichia coli; Fc receptors; ITAM; Immunotherapy; Inflammation; Phagocytosis; Sepsis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Bacterial / immunology*
  • Escherichia coli
  • Escherichia coli Infections / immunology*
  • Escherichia coli Proteins / immunology*
  • Humans
  • Ligands
  • Membrane Transport Proteins / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Peptide Library
  • Phagocytes / immunology
  • Phagocytosis*
  • Receptors, IgG / immunology*
  • Sepsis / prevention & control
  • Signal Transduction

Substances

  • Antigens, Bacterial
  • Escherichia coli Proteins
  • Ligands
  • Membrane Transport Proteins
  • Peptide Library
  • Receptors, IgG
  • WzxE protein, E coli
  • enterobacterial common antigen